GRAY MATTERS: Be aware of cognitive side effects from common drugs

Dozens of painkillers, antihistamines and psychiatric medications -- everything from over-the-counter staples like Benadryl, Dramamine and Tylenol PM to prescription drugs such as Paxil and oxybutynin -- have been linked to memory loss, cognitive impairment and risk of death in seniors.

"There's the relative notion that if it is over-the-counter, it has to be super safe and effective," said Patrick Cloney of Cloney's Pharmacy. "This is a good reminder that people need to be aware of exactly what is in their meds and that medicine is constantly evolving and will continue to do so."

"People need to become educated about staying healthy and not always taking a pill," said Ramona Lima of Lima's Pharmacy. "That sounds odd being a pharmacist and pills being my livelihood, but pills are not the answer all the time."

"Chelsea" is a case in point. The residential care specialist requested anonymity in talking about her past use of Benadryl and its active ingredient, diphenhydramine, to ease post-menopausal symptoms.

"Benadryl is the drug of choice for many post-menopausal women because it helps you sleep," she said.

Over a period of four years, the mother of three went from one Benadryl a night to the recommended maximum of four, then couldn't find her car in a parking lot despite walking by it twice.

"I went back to the office absolutely hysterical," she recalled. "I thought for sure I had dementia. That was the trigger for me."

A self-administered mini-mental test didn't ease her fears. Then, as part of her job in the world of senior care, she learned of studies that suggested Benadryl and other anticholinergic drugs might not be good for people with dementia or the cognitively impaired.

"I stopped taking it and asked for a different type of sleep medication," she said.

That was early last year.

"I'm 62 now and my memory has increased dramatically, so much so that my kids noticed and I hadn't even spoken to them about it," she said.

"You know how you have a conversation with the kids and they say, 'Don't you remember? I told you about something or other.' I'd be totally blank. Now, it's a click and I remember. I can find my car in the parking lot, too."

Although Chelsea's story is anecdotal, it's also a reminder of the importance of assessing personal changes when starting new medications, giving pharmacists or health care providers a list of over-the-counter medications that are self-prescribed, and staying abreast of medical research.

Residential and skilled nursing facilities routinely track and update patient medication lists for hospitals and health care providers and take part in continuing education. But individuals and family members who provide support to aging loved ones living independently may not be as good at sharing, updating and assessing the use and impact of over-the-counter anticholinergic medications.

Anticholinergics block -- on purpose or as a side effect -- a chemical messenger known as acetylcholine that serves a range of tasks in the body including memory and cognitive function.

"Anticholinergics aren't even recommended in the elderly because the older you get, the less viable your body can be. Things start to slow down and continue to do that as part of the aging process," Lima said. "It's all about determining how a drug is going to benefit the patient in the long run compared to the adverse effect profile over that time."

Research results linking anticholinergics and cognitive impairment is relatively recent and ongoing.

In its online edition for June 24, 2011, the Journal of American Geriatrics Society published a two-year study of 13,000 British men and women age 65 and older that found that those taking more than one anticholinergic scored lower on cognitive function tests than those who did not use the drugs.

The study also found that the death rate for heavy users was 68 percent higher, making it the first to link anticholinergics to premature death.

"Our findings make it clear that clinicians need to review the cumulative anticholinergic burden in people presenting with cognitive impairment to determine if the drugs are causing decline in mental status," said co-author Dr. Malaz Boustani, research director for the Healthy Aging Brain Center at Indiana University, in a media release.

"Physicians should review with older patients all the over-the-counter and prescription drugs they are taking to determine exposure."

Each drug taken by study participants was ranked based on its anticholinergic burden with 0 for no effect, 1 for mild effect, 2 for moderate effect and 3 for severe effect.

The U.S. National Institute of Aging supported Dr. Boustani's development of the Anticholinergic Burden Scale, which can be found online. The listing features 35 drugs with a severe anticholinergic burden -- among them diphenhydramine, which is contained in Benadryl, Dramamine, Excedrin PM and Tylenol PM.

Twelve have a moderate burden and 36 a low burden.

One in five participants who took drugs with a total anticholinergic burden (ACB) of 4 or more had died by the end of the study compared to 7 percent of those taking no anticholinergic drugs. For every additional ACB point scored, the odds of dying increased by 26 percent.

An ACB of 3 or more is considered "clinically relevant" and the increased risks were shown to be cumulative based on the drug and dosage.

"You have to monitor the effect. You have to have accurate, up-to-date medication lists. You have to take a pro-active role in your own health care. It is all about education and awareness," Lima said.

"Knowledge is power, but sometimes I wish we didn't know," said Mark Lamers, psychologist and mental health expert for Humboldt County's Department of Health and Human Services. He's ousted Benadryl from his medicine cabinet, opting for Claritin instead.

"You think over-the-counter is safe, and for all intents and purposes, it is. But at the same time, too much is never a good thing," Lima said.

"Absolutely no medicine is free of side effects," geriatric nurse practitioner Tim Haskett said. "You have to balance the side effects with the benefits and other options for treatment. There's subtlety in these things. The best thing to do is to talk to your provider and sort it out."

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Area 1 Agency on Aging commissioned Carol Harrison to produce this story.